Nanophase hydroxyapatite and poly(lactide-co-glycolide) composites promote human mesenchymal stem cell adhesion and osteogenic differentiation in vitro

  • Jaclyn Lock
  • Thanh Yen Nguyen
  • Huinan LiuEmail author


Human mesenchymal stem cells (hMSCs) typically range in size from 10 to 50 μm and proteins that mediate hMSC adhesion and differentiation usually have a size of a few nanometers. Nanomaterials with a feature size smaller than 100 nm have demonstrated the unique capability of promoting osteoblast (bone forming cell) adhesion and long-term functions, leading to more effective bone tissue regeneration. For new bone deposition, MSCs have to be recruited to the injury or disease sites and then differentiate into osteoblasts. Therefore, designing novel nanomaterials that are capable of attracting MSCs and directing their differentiation is of great interest to many clinical applications. This in vitro study investigated the effects of nanophase hydroxyapatite (nano-HA), nano-HA/poly(lactide-co-glycolide) (PLGA) composites and a bone morphogenetic protein (BMP-7) derived short peptide on osteogenic differentiation of hMSCs. The short peptide was loaded by physical adsorption to nano-HA or by dispersion in nanocomposites and in PLGA to determine their effects on hMSC adhesion and differentiation. The results showed that the nano-HA/PLGA composites promoted hMSC adhesion as compared to the PLGA controls. Moreover, nano-HA/PLGA composites promoted osteogenic differentiation of hMSCs to a similar extent with or without the presence of osteogenic factors in the media. In the MSC growth media without the osteogenic factors, the nanocomposites supported greater calcium-containing bone mineral deposition by hMSC than the BMP-derived short peptide alone. The nanocomposites provided promising alternatives in controlling the adhesion and differentiation of hMSCs without osteogenic factors from the culture media, and, thus, should be further studied for clinical translation and the development of novel nanocomposite-guided stem cell therapies.


Osteogenic Differentiation Calcium Deposition Osteogenic Medium Peptide Control PLGA Scaffold 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The author would like to thank the NSF BRIGE award (CBET 1125801), Burroughs Wellcome Fund (1011235), and the University of California for financial support.


  1. 1.
    Liu H, Slamovich EB, Webster TJ. Increased osteoblast functions among nanophase titania/poly(lactide-co-glycolide) composites of the highest nanometer surface roughness. J Biomed Mater Res A. 2006;78(4):798–807.Google Scholar
  2. 2.
    Liu H, Yazici H, Ergun C, Webster TJ, Bermek H. An in vitro evaluation of the Ca/P ratio for the cytocompatibility of nano-to-micron particulate calcium phosphates for bone regeneration. Acta Biomater. 2008;4(5):1472–9.CrossRefGoogle Scholar
  3. 3.
    Ergun C, Liu H, Halloran JW, Webster TJ. Increased osteoblast adhesion on nanograined hydroxyapatite and tricalcium phosphate containing calcium titanate. J Biomed Mater Res A. 2007;80(4):990–7.Google Scholar
  4. 4.
    Liu H, Webster TJ. Mechanical properties of dispersed ceramic nanoparticles in polymer composites for orthopedic applications. Int J Nanomed. 2010;5:299–313.Google Scholar
  5. 5.
    Liu H, Webster TJ. Nanomedicine for implants: a review of studies and necessary experimental tools. Biomaterials. 2006;28(2):354–69.CrossRefGoogle Scholar
  6. 6.
    Wang EA, Rosen V, D’Alessandro JS, Bauduy M, Cordes P, Harada T, Israel DI, Hewick RM, Kerns KM, LaPan P, et al. Recombinant human bone morphogenetic protein induces bone formation. Proc Natl Acad Sci USA. 1990;87(6):2220–4.CrossRefGoogle Scholar
  7. 7.
    Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA. Novel regulators of bone formation: molecular clones and activities. Science. 1988;242(4885):1528–34.CrossRefGoogle Scholar
  8. 8.
    Glassman SD, Carreon LY, Campbell MJ, Johnson JR, Puno RM, Djurasovic M, Dimar JR. The perioperative cost of infuse bone graft in posterolateral lumbar spine fusion. Spine J. 2008;8(3):443–8.CrossRefGoogle Scholar
  9. 9.
    Smoljanovic T, Bicanic G, Bojanic I. Update of comprehensive review of the safety profile of bone morphogenetic protein in spine surgery. Neurosurgery. 2010;66(5):E1030. author reply E1030.CrossRefGoogle Scholar
  10. 10.
    Benglis D, Wang MY, Levi AD. A comprehensive review of the safety profile of bone morphogenetic protein in spine surgery. Neurosurgery 2008;62(5 Suppl 2):ONS423-31; discussion ONS431.Google Scholar
  11. 11.
    Haid RW, Jr, Branch CL, Jr, Alexander JT, Burkus JK. Posterior lumbar interbody fusion using recombinant human bone morphogenetic protein type 2 with cylindrical interbody cages. Spine J. 2004;4(5):527–38. discussion 538-9.CrossRefGoogle Scholar
  12. 12.
    McKay WF, Peckham SM, Badura JM. A comprehensive clinical review of recombinant human bone morphogenetic protein-2 (INFUSE (R) Bone Graft). Int Orthop. 2007;31(6):729–34.CrossRefGoogle Scholar
  13. 13.
    Chen Y, Webster TJ. Increased osteoblast functions in the presence of BMP-7 short peptides for nanostructured biomaterial applications. J Biomed Mater Res A. 2009;91(1):296–304.Google Scholar
  14. 14.
    Liu H, Webster TJ. Ceramic/polymer nanocomposites with tunable drug delivery capability at specific disease sites. J Biomed Mater Res A. 2010;93(3):1180–92.Google Scholar
  15. 15.
    Lock J, Liu H. Nanomaterials enhance osteogenic differentiation of human mesenchymal stem cells similar to a short peptide of BMP-7. Int J Nanomed. 2011;6:2769–77.Google Scholar
  16. 16.
    Sato M, Sambito MA, Aslani A, Kalkhoran NM, Slamovich EB, Webster TJ. Increased osteoblast functions on undoped and yttrium-doped nanocrystalline hydroxyapatite coatings on titanium. Biomaterials. 2006;27(11):2358–69.CrossRefGoogle Scholar
  17. 17.
    Ioku K, Yoshimura M. Stoichiometric apatite fine single crystals by hydrothermal synthesis. Phosphorus Res Bull. 1991;1:15–20.Google Scholar
  18. 18.
    Somiya S, Ioku K, Yoshimura M. Hydrothermal synthesis and characterization of fine apatite crystals. Magnes Sci Technol Appl. 1988;34:371–8.Google Scholar
  19. 19.
    Hing KA, Revell PA, Smith N, Buckland T. Effect of silicon level on rate, quality and progression of bone healing within silicate-substituted porous hydroxyapatite scaffolds. Biomaterials. 2006;27(29):5014–26.CrossRefGoogle Scholar
  20. 20.
    Coathup M, Smith N, Kingsley C, Buckland T, Dattani R, Ascroft P, Blumn G. Impaction grafting with a bone-graft substitute in a sheep model of revision hip replacement. J Bone Joint Surg Br. 2008;90B(2):246–53.Google Scholar
  21. 21.
    Siffert RS. The role of alkaline phosphatase in osteogenesis. J Exp Med. 1951;93(5):415–29.CrossRefGoogle Scholar
  22. 22.
    Sato M, Aslani A, Sambito MA, Kalkhoran NM, Slamovich EB, Webster TJ. Nanocrystalline hydroxyapatite/titania coatings on titanium improves osteoblast adhesion. J Biomed Mater Res A. 2008;84(1):265–72.Google Scholar
  23. 23.
    Balasundaram G, Sato M, Webster TJ. Using hydroxyapatite nanoparticles and decreased crystallinity to promote osteoblast adhesion similar to functionalizing with RGD. Biomaterials. 2006;27(14):2798–805.CrossRefGoogle Scholar
  24. 24.
    Zhang R, Ma PX. Degradation behavior of porous poly(a-hydroxy acids)/hydroxyapatite composite scaffolds. American Chemical Society. 2000;41(2):1618–19.Google Scholar
  25. 25.
    Noohom W, Jack KS, Martin D, Trau M. Understanding the roles of nanoparticle dispersion and polymer crystallinity in controlling the mechanical properties of HA/PHBV nanocomposites. Biomed Mater. 2009;4(1):015003.CrossRefGoogle Scholar
  26. 26.
    Palin E, Liu HN, Webster TJ. Mimicking the nanofeatures of bone increases bone-forming cell adhesion and proliferation. Nanotechnology. 2005;16(9):1828–35.CrossRefGoogle Scholar
  27. 27.
    Liu HN, Slamovich EB, Webster TJ. Increased osteoblast functions on nanophase titania dispersed in poly-lactic-co-glycolic acid composites. Nanotechnology. 2005;16(7):S601–8.CrossRefGoogle Scholar
  28. 28.
    Senta H, Bergeron E, Drevelle O, Park H, Faucheux N. Combination of synthetic peptides derived from bone morphogenetic proteins and biomaterials for medical applications. Can J Chem Eng. 2011;89(2):227–39.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of BioengineeringUniversity of California, RiversideRiversideUSA
  2. 2.The Materials Science and Engineering ProgramUniversity of California, RiversideRiversideUSA
  3. 3.Stem Cell CenterUniversity of California, RiversideRiversideUSA

Personalised recommendations